This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Although there has been an overall decline in cardiovascular disease (CVD) mortality over the past halfcentury, racial/ethnic minorities continue to suffer a disproportionate burden of lives lost. This increased burden of CVD mortality involves social, behavioral and genetic factors that predispose to CVD risk factors such as obesity, diabetes and hypertension. Recent studies have implicated deficiencies in Vitamin D (Vit-D) in the pathogenesis of a variety of disorders including cancer, diabetes and hypertension. Indeed, Vit-D insufficiency affects nearly 50% of the US population and 80% of African-Americans. A growing body of evidence suggests that the increased susceptibility to Vit-D deficiency among African-Americans reflects the interplay between environmental, social, behavioral and genetic factors. Unfortunately, the field has lacked an integrated, multi-level model that systematically characterizes the genetic-behavioral-social interactions that influence Vit-D metabolism and contribute to hypovitaminosis in African-Americans. Moreover, it remains unclear whether clinical interventions that normalize Vit-D homeostasis in African-Americans will ameliorate health disparity conditions such as hypertension and CVD. Our multi-disciplinary team will take a multi-level approach to address this challenging and important problem. Our working model hypothesizes that nutrient-genetic interactions that have transpired during the population history of individuals of African ancestry have resulted in a distinctive set of alleles that modify the response to sun exposure, the regulation of Vit-D metabolism and the nutrigenomic responses to Vit-D. Moreover, these intrinsic biological pathways are further modified by the influence of behavioral factors and the unique social-environmental conditions experienced by African-Americans. We will assess these multilevel interactions by pursuing the following specific aims: Aim I: To characterize the interactions between genetic, behavioral, social and environmental factors on dietary Vit-D intake and sun exposure as determinants of Vit-D levels in African- Americans. Aim II: To characterize the gene-environment interactions that influence the nutrigenomic response to Vit-D supplementation on the Vit-D-Parathyroid Hormone level relationship in African-Americans. PUBLIC HEALTH RELEVANCE: Due to dietary habits and other factors, most Americans are relatively deficient in Vitamin D. Recent evidence suggests that Vitamin D deficiency may predispose to cancer, diabetes and heart disease. African-Americans are particularly vulnerable to this condition. The proposed project will address the causes of this health disparity and refine the therapeutic strategy for correcting this major public health problem.